WO2004041317A1 - Self-folding polymer microparticles - Google Patents
Self-folding polymer microparticles Download PDFInfo
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- WO2004041317A1 WO2004041317A1 PCT/US2003/036066 US0336066W WO2004041317A1 WO 2004041317 A1 WO2004041317 A1 WO 2004041317A1 US 0336066 W US0336066 W US 0336066W WO 2004041317 A1 WO2004041317 A1 WO 2004041317A1
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J13/00—Colloid chemistry, e.g. the production of colloidal materials or their solutions, not otherwise provided for; Making microcapsules or microballoons
- B01J13/02—Making microcapsules or microballoons
- B01J13/04—Making microcapsules or microballoons by physical processes, e.g. drying, spraying
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6921—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere
- A61K47/6927—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere the form being a solid microparticle having no hollow or gas-filled cores
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
- A61K9/0097—Micromachined devices; Microelectromechanical systems [MEMS]; Devices obtained by lithographic treatment of silicon; Devices comprising chips
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1635—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1641—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers
- A61K9/1647—Polyesters, e.g. poly(lactide-co-glycolide)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1682—Processes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1682—Processes
- A61K9/1694—Processes resulting in granules or microspheres of the matrix type containing more than 5% of excipient
Definitions
- the present invention relates generally to methods for fabricating microparticles for use in scientific and/or medical applications and more specifically to a method for creating polymer microparticles having certain three-dimensional characteristics.
- Microparticulate systems that utilize one or more polymers are widely used for biomedical applications such as drug delivery, bio-analysis, and clinical diagnosis.
- the particles produced by conventional manufacturing methods are typically limited to a spherical shape, relatively wide size distributions, and symmetrical monolithic or core-shell structures. While spherical microparticles are useful for certain applications such as drug delivery, non-spherical particles may have more desirable characteristics. For example, discrete control of particle geometry may facilitate more precise bio-analysis and controlled drug delivery because the shape of a particle can be tailored to function more effectively under certain predefined conditions. Thus, there is a need for a method for fabricating microparticles in a variety of three-dimensional shapes and geometric configurations.
- Microfabrication techniques conventionally used for making integrated circuits have been utilized to create microparticles by combining silicon dioxide or polymethylmethacrylate (PMMA) and a photo-sensitive polymer. These techniques can be used to create microparticles having a precise shape, uniform size and specifically designed structures and surface chemistries, thereby making them suitable for use as drug-carrying vehicles.
- these techniques are limited in that they (i) require the use of photolithography to create every particle and (ii) are compatible with only certain materials.
- the rigorous conditions, including highly aggressive solutions and elevated temperatures, which are used to release fabricated microparticles into solution may damage fragile compounds that have been incorporated into the microparticles.
- photolithographic techniques for microfabrication of microparticles there are significant limitations to using known photolithographic techniques for microfabrication of microparticles.
- Soft lithography is a collective term that refers to a group of non-photolithographic microfabrication techniques that employ elastomeric stamps having certain three dimensional relief features to generate micro-structures and even nano-structures.
- Soft lithography is a more detailed description of soft lithography is found in Xia and Whitesides, Annual Review of Materials
- the exemplary embodiment of which provides a method for forming three-dimensional polymeric particulate microstructures through self-folding of thin-film microparticles.
- self-folding of two-dimensional polymeric precursors produces various three-dimensional particulate microstructures.
- Dumpling-like microstructures with oil cores and polymer coats are prepared by an interfacial-tension driven self-folding method.
- Roll-like and bowl-shaped hydrogel microstructures are fabricated by self-folding, induced by differential volume shrinkage. Curled microstructures are produced by self-folding that is the result of a two-polymer or bilayer method.
- FIG. la is a schematic illustration of the embodiment of the present invention that utilizes an interfacial tension driven method for fabricating dumpling-like oil-in-PPMA three- dimensional microstructures.
- FIG. 2a is a schematic illustration of the embodiment of the present invention that utilizes a property gradient method for fabricating PHEMA and PMAA 3-D microstructures.
- FIG. 2c is an optical micrograph of the bowl-shaped PMAA microstructures fabricated by the method of FIG. 2a in buffer solution with pH of 10 and formed from 30 ⁇ m- wide square micropads.
- the upper left insert of FIG. 2c shows a 30 ⁇ m-wide square micropad before released into solution.
- FIG. 3 a is a schematic illustration of the embodiment of the present invention that utilizes a bilayer method for fabricating curled PMAA/PLGA bilayer microstructures.
- FIG. 4a is a schematic illustration of the embodiment of the present invention that fabricates three-dimensional microstructures by a method that includes double stamping of foldable bilayer strips.
- FIG. 4b is an optical micrograph of three-dimensional structures made from foldable
- FIG. 5 a is an optical micrograph of a 40 ⁇ m wide square PMAA micropad on PVA.
- FIG. 5b is a series of optical micrograph of microstructures formed by self-folding of released PMAA micropads in neutral water.
- FIG. 5c is a series of optical micrographs of microstructures formed by self-folding of released PMAA micropads in buffer solution having a pH of 10.
- interfacial tension driven method With reference to FIGS, la-b, this method involves the following steps for creating self-folding polymer microparticles:
- polymeric micropads are printed on a substrate that has been coated with a dissolvable "sacrificial" layer of material.
- a dissolvable "sacrificial" layer of material 40 ⁇ m- wide square poly (propyl methacrylate) (PPMA) micropads are printed on a chitosan-coated glass slide by a technique known as microContact Hot Printing (" ⁇ CHP") which utilizes a poly (dimethyl siloxane) (PDMS) stamp.
- ⁇ CHP microContact Hot Printing
- PDMS poly (dimethyl siloxane)
- a thin layer of oil is applied to the substrate such that the oil only accumulates on the micropads.
- food-grade soybean oil is applied to the slide, leaving oil droplets only on the PPMA micropads due, presumably, to the polarity differences between oil, PPMA and chitosan.
- a solvent is added to dissolve the sacrificial layer and release the printed micropads into solution.
- aqueous acetic acid solution is added to release the micropads by dissolving the chitosan sacrificial layer. The released micropads fold over the oil droplets spontaneously, forming the dumpling-like microstructures shown in the optical micrograph of FIG. lb.
- the selective wetting of the micropads by the oil is a result of minimization of interfacial energy of the system due to low surface tensions of PPMA and oil and the high surface tension of chitosan.
- the folding of the micropads is most-likely driven by free-energy minimization as water replaces air in the system. Since the oil-water interfacial tension is larger than that of oil-air and PPMA-water, the oil droplets that initially spread on the micropads tend to shrink into a spherical shape to minimize their interfacial area in contact with water. Also, due to the strong adhesion between oil and PPMA, and the response of the micropads, the oil droplets force the released micropads to fold around them.
- the final structures are dumpling-like microcapsules with oil cores and PPMA outer coats.
- the self-folding polymer system of this first embodiment includes an oil as a shrinking liquid with low surface tension, micropads formed from PPMA having low surface tension that allows the oil wet the micropads, chitosan as a dissolvable layer with high surface tension that prevents the oil from wetting the sacrificial layer and allows the oil to accumulate on micropads, and water as a solvent with high surface tension that dissolves the chitosan and induces the shrinkage of the oil droplets.
- the oil/PPMA/chitosan water system is a LST (low surface tension)/LST/HST (high surface tension)/HST system. Other materials can be used with this method if they have these general characteristics.
- this HST/HST/LST/LST system is ideally suited for fabrication of dumpling-like microstructures due to the use of an aqueous solution as a shrinking liquid, a hydrophilic polymer for the micropads, a hydrophobic dissolvable layer, and a hydrophobic solvent to release the micropads and induce self-folding of the microparticles.
- a second embodiment of the method of the present invention is referred to as the "property gradient method.” This embodiment induces self-folding of hydrogel micropads to form three dimensional microstructures. With reference to FIGS. 2a-c, this method involves the following steps for creating self-folding polymer microparticles:
- polymeric (i.eterrorism hydrogel) micropads are printed on a substrate coated with a dissolvable or "sacrificial" layer using a PDMS stamp as described above.
- a PDMS stamp as described above.
- poly (hydroxyethyl methacrylate) (PHEMA) and poly (methacrylic acid) (PMAA) are used as the hydrogel component; however, other volume- changeable hydrogels are also compatible with this method.
- the PDMS stamp used for preparing PHEMA microstructures includes 40 ⁇ m-wide and 1.4 ⁇ m-deep square microwells separated by 10 ⁇ m-wide ridges.
- the PDMS stamp used for preparing the PMAA microstructures includes 30 ⁇ m-wide and 1.1 ⁇ m-deep square microwells separated by 20 ⁇ m-wide ridges.
- Monomer hydrogel precursor solutions are typically cured (partially) before transfer to the wells of the PDMS stamp. Pre-curing increases the viscosity of the pre-polymer layers, thereby making them less likely to rupture in the wells. Partially curing the monomer solutions also lowers the evaporation rate of volatile liquids such as the MAA monomer in the shallow wells of the stamp.
- the HEMA monomer (98.6 wt%) with Irgacure 651 (2, 2-dimethoxy-2-phenylacetophenone, 1.4 wt%) as photoinitiator in a closed bottle was exposed to UV for 4 minutes until a viscous medium was obtained.
- the crosslinking agent TEGDMA (triethylene glycol dimethacrylate) with a molar ratio of 2.4 : 100 to the initial HEMA monomer was then added.
- the MAA monomer (53.2 wt%), solvent DMSO (46.1 wt%), and photoinitiator Irgacure 651 (0.7 wt%) was exposed to UV for 8 minutes in a closed bottle.
- the crosslinking agent TEGDMA with a molar ratio of 5.2 : 100 to the initial MAA monomer was then added.
- the mixed viscous solutions were placed in the microwells by discontinuous wetting and further exposed to UV for 20 minutes under blowing nitrogen.
- the fully cured polymer in the microwells was then printed as micropads onto a poly (vinyl alcohol) (PVA)-coated glass slide.
- PVA poly (vinyl alcohol)
- a solvent is added to dissolve the sacrificial layer and release the micropads into solution.
- the released micropads fold spontaneously or fold in the presence of a certain stimulus such as a change in pH.
- a certain stimulus such as a change in pH.
- water and a buffer solution with a pH of 4.0 was added to dissolve the polyvinyl alcohol (PVA) sacrificial layer.
- FIG. 2c is an optical micrograph of the bowl-shaped PMAA microstructures in buffer solution with pH of 10 and formed from 30 ⁇ m-wide square micropads.
- the upper left insert of FIG. 2c shows a 30 ⁇ m- wide square micropad before released into solution.
- the spontaneous folding of the microparticles in this embodiment is likely due to a heterogeneous volume change along the thickness direction and/or in the plane of the micropads due to property gradients along the thickness direction and/or in the plane of the micropads.
- the top surface of the micropads After being printed on the substrate, the top surface of the micropads will have higher "molded-in" stresses. Relaxation of this gradient stress is expected to cause upward- folding of the micropads.
- uniaxial folding of individual micropads is required. Relaxation of anisotropic stress in the dragging direction may be responsible for the uniaxial folding of the micropads.
- Non-uniform crosslinking density across the plane of micropads may be responsible for the formation of bowl-shaped PMAA microstructures.
- a third embodiment of the method of the present invention is referred to as the "bilayer method.”
- this method involves the following steps for creating self-folding polymer microparticles: First, bilayer polymeric micropads are printed on a substrate coated with a dissolvable or "sacrificial" layer using a PDMS stamp as described in U.S. Patent Application Serial No. 10/656,661. Second, a solvent is added to dissolve the sacrificial layer and release the micropads into solution. The released micropads curl spontaneously or curl in the presence of a certain stimulus such as a change in pH. In the exemplary embodiment of FIGS.
- FIG. 3a-b 40 ⁇ m-wide square microparticles were fabricated using a PMAA/PLGA (polylactic-co- glycolic acid) bilayer.
- the spontaneous curling of the microparticles in this embodiment is likely due to a differential volume change of the two polymer layers.
- the PMAA layer swells in water while
- PLGA does not have volume or shape change, leading to the slight curling of the micropads.
- the final three-dimensional geometries of the microstructures fabricated by the methods of the present invention can be further controlled by pre-designing that lateral shapes of the "two dimensional" (i.e., flat) micropads.
- the three general embodiments of the method described herein, as well as the techniques disclosed in U.S. Patent Application Serial No. 10/656,661 can be combined to fabricate microstructures having more versatile structures. For example, using foldable bilayer rectangular micropads and double the stamping technique, microstructures in shown in FIG. 4a can be fabricated.
- FIG. 4b is an optical micrograph of the macroversion of the three-dimensional structures made from foldable PMAA/PHEMA bilayer strips according to this method.
- FIG. 5a is an optical micrograph of a 40 ⁇ m wide square PMAA micropad on
- FIG. 5b is a series of optical micrograph of microstructures formed by self-folding of released PMAA micropads in neutral water.
- FIG. 5c is a series of optical micrographs of microstructures formed by self-folding of released PMAA micropads in buffer solution having a pH of 10.
- PPMA was obtained from Monomer-Polymer & Dajac Laboratory (Feasterville, PA).
- TEGDMA triethyleneglycol dimethacrylate
- Irgacure 651 2-Dimethoxy-2- phenylacetophenone
- acetone HEMA
- DMSO DMSO
- chitosan was obtained from Sigma- Aldrich.
- PVA 88 mol % hydrolyzed, 25,000Da
- PDMS T2
- Buffer solutions with a pH 4.0 (SB 101-500) and glass slides were purchased from Fisher Scientific.
- a Nikon TMS inverted optical microscope and a Fujifilm Finepix 2600 digital camera were used to take micrographs.
- a hot plate was used to heat glass slides and the temperature was measured by a thermocouple.
- the UV source was a UV/WL table (Vilber Lourmat, Marne- La-Vallee, France) producing 312 ran UV light. UV-curing was carried out in a box under blowing nitrogen.
- the polymer microparticles of the present invention are useful for a variety of applications. Microparticles made by the interfacial tension driven method may be used for drug encapsulation. When oil is encapsulated in hydrophobic micropads, oil-soluble drugs can be dissolved in the encapsulated oil droplets, whereas water-soluble drugs can be dispersed in the form of solid powder or emulsion in the encapsulated oil droplets.
- water-soluble drugs can be dissolved or dispersed in the form of liposomes in the encapsulated aqueous droplets, whereas oil-soluble drugs can be dispersed in the form of emulsion in the encapsulated aqueous droplets.
- All three embodiments of the present invention may be used to encapsulate cells for applications such as carrying and protecting cells in bioreactor and serving as a three- dimensional scaffold for tissue engineering.
- self-folding can be induced by tensile stress generated by the cells growing on micropads.
- the tensile stress generated by cells growing on micropads is not necessary because micropads can fold spontaneously and encapsulate cells. Therefore, cells do not have to grow on the micropads.
- Three-dimensional microstructures with discretely controlled geometries may be useful for drug delivery by the pulmonary route.
- the methods disclosed herein may be used to make environment-sensitive polymer-based microdevices having three dimensional structures that change their shape in response to environmental stimuli. While the above description contains many specificities, these should not be construed as limitations on the scope of the invention, but rather as exemplification of certain preferred embodiments. Numerous other variations of the present invention are possible, and is not intended herein to mention all of the possible equivalent forms or ramifications of this invention. Various changes may be made to the present invention without departing from the scope or spirit of the invention.
Abstract
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Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
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AU2003287705A AU2003287705A1 (en) | 2002-11-05 | 2003-11-04 | Self-folding polymer microparticles |
CA002504842A CA2504842A1 (en) | 2002-11-05 | 2003-11-04 | Self-folding polymer microparticles |
EP03781910A EP1560611A1 (en) | 2002-11-05 | 2003-11-04 | Self-folding polymer microparticles |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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US42409202P | 2002-11-05 | 2002-11-05 | |
US60/424,092 | 2002-11-05 |
Publications (1)
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WO2004041317A1 true WO2004041317A1 (en) | 2004-05-21 |
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PCT/US2003/036066 WO2004041317A1 (en) | 2002-11-05 | 2003-11-04 | Self-folding polymer microparticles |
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US (1) | US7364675B2 (en) |
EP (1) | EP1560611A1 (en) |
AU (1) | AU2003287705A1 (en) |
CA (1) | CA2504842A1 (en) |
WO (1) | WO2004041317A1 (en) |
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KR20060014179A (en) * | 2004-08-10 | 2006-02-15 | 삼성에스디아이 주식회사 | Method for forming emitter and method for manufacturing field emission device using the same |
US7655244B2 (en) * | 2005-02-01 | 2010-02-02 | Allergan, Inc. | Targeted delivery of botulinum toxin for the treatment and prevention of trigeminal autonomic cephalgias, migraine and vascular conditions |
US8475924B2 (en) * | 2007-07-09 | 2013-07-02 | E.I. Du Pont De Nemours And Company | Compositions and methods for creating electronic circuitry |
CN101809446B (en) | 2007-09-27 | 2013-11-27 | 株式会社三养生物制药 | Sol-gel phase-reversible hydrogel templates and uses thereof |
CN102099462B (en) * | 2008-07-14 | 2013-09-18 | 皇家飞利浦电子股份有限公司 | Process for providing an assembly of cell microcarriers |
US7763173B1 (en) * | 2009-01-12 | 2010-07-27 | Koopmans Richard J | Method for remediating solids in waste lifting stations |
US8795727B2 (en) | 2009-11-09 | 2014-08-05 | Spotlight Technology Partners Llc | Fragmented hydrogels |
US9700650B2 (en) | 2009-11-09 | 2017-07-11 | Spotlight Technology Partners Llc | Polysaccharide based hydrogels |
KR20110100405A (en) * | 2010-03-04 | 2011-09-14 | 전북대학교산학협력단 | Process for the preparation of 3d folding actuators |
US9308219B2 (en) * | 2011-06-30 | 2016-04-12 | Collagen Matrix, Inc. | Flat self-curling permeable sheet membrane |
KR20150077413A (en) | 2012-09-17 | 2015-07-07 | 프레지던트 앤드 펠로우즈 오브 하바드 칼리지 | Soft exosuit for assistance with human motion |
EP2967816A4 (en) * | 2013-03-12 | 2016-11-16 | Carol Livermore-Clifford | Deterministic manufacturing process for creating 3d living tissues based on 2d directed assembly and origami techniques |
WO2014194257A1 (en) | 2013-05-31 | 2014-12-04 | President And Fellows Of Harvard College | Soft exosuit for assistance with human motion |
CA2932883A1 (en) | 2013-12-09 | 2015-06-18 | President And Fellows Of Harvard College | Assistive flexible suits, flexible suit systems, and methods for making and control thereof to assist human mobility |
EP3128963A4 (en) | 2014-04-10 | 2017-12-06 | President and Fellows of Harvard College | Orthopedic device including protruding members |
US11590046B2 (en) | 2016-03-13 | 2023-02-28 | President And Fellows Of Harvard College | Flexible members for anchoring to the body |
EP3487666A4 (en) | 2016-07-22 | 2020-03-25 | President and Fellows of Harvard College | Controls optimization for wearable systems |
WO2018170170A1 (en) * | 2017-03-14 | 2018-09-20 | President And Fellows Of Harvard College | Systems and methods for fabricating 3d soft microstructures |
US10821565B2 (en) | 2017-06-02 | 2020-11-03 | Regents Of The University Of Minnesota | Method of manufacturing a remote-controlled micro-scale three-dimensional self-assembly |
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- 2003-11-04 WO PCT/US2003/036066 patent/WO2004041317A1/en not_active Application Discontinuation
- 2003-11-04 AU AU2003287705A patent/AU2003287705A1/en not_active Abandoned
- 2003-11-04 CA CA002504842A patent/CA2504842A1/en not_active Abandoned
- 2003-11-04 EP EP03781910A patent/EP1560611A1/en not_active Withdrawn
- 2003-11-04 US US10/700,715 patent/US7364675B2/en active Active
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US5512131A (en) * | 1993-10-04 | 1996-04-30 | President And Fellows Of Harvard College | Formation of microstamped patterns on surfaces and derivative articles |
US20030129654A1 (en) * | 1999-04-15 | 2003-07-10 | Ilya Ravkin | Coded particles for multiplexed analysis of biological samples |
Also Published As
Publication number | Publication date |
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CA2504842A1 (en) | 2004-05-21 |
US20040191321A1 (en) | 2004-09-30 |
EP1560611A1 (en) | 2005-08-10 |
US7364675B2 (en) | 2008-04-29 |
AU2003287705A1 (en) | 2004-06-07 |
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